Ultrastructural analysis shows persistence of adhesion and tight junction proteins in mature human hair

The differentiation of cells composing mature human hairs produces layers with different corneous characteristics that would tend to flake away one from another,as in the corneous layer of the epidermis,without anchoring junctions.It is likely that cell junctions established in the forming cells of the hair bulb are not completely degraded like in the corneous layer of the epidermis but instead remain in the hair shaft to bind mature cuticle,cortex,and medulla cells into a compact hair shaft.During cell differentiation in hairs,cell junctions seem to disappear,and little is known about the fate of junctional proteins present in the mature human hair shaft.The present ultrastructural immunogold study has detected some marker proteins of adhesion junction(cadherin and beta-catenin)and tight junctions(occludin and cingulin)that are still present in cornified hairs where numerous isopeptide bonds are detected,especially in the medulla.This qualitative ultrastructural study indicates that aside from the cell membrane complex,a long corneo-desmosome bonding cortex and cuticle cells,also sparse adherens and tight junction remnants are present.It is suggested that the cornification of these junctions with the incorporation of their proteins within the mature corneous material of the hair shaft likely contributes to maintaining the integrity of the mature hair.This information will also allow us to evaluate the effects of different chemical components present in hair formulations and stains on these junctional proteins and the consequent integrity of the hair shaft.

Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma

Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagnosis biomarkers and pharmacological targets.Junctional adhesion molecule-like protein(JAML)was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD.However,the effect of kaempferol on JAML is still unknown.Methods:Small interfering RNA was used to knockdown JAML expression.The cell viability was determined using the cell counting kit-8 assay.The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay.The migration and invasion of LUAD cells were evaluated by transwell assays.Molecular mechanisms were explored by Western blotting.Results:JAML knockdown suppressed proliferation,migration and invasion of LUAD cells,and JAML deficiency restrained epithelial-mesenchymal transition(EMT)via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.Using a PI3K activator(740Y-P),rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway.Kaempferol also inhibited proliferation,migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway.Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells.Kaempferol exerted anticancer effects by targeting JAML.Conclusion:JAML is a novel target for kaempferol against LUAD cells.

Hemicentins:What have we learned from worms?

Hemicentins are conserved extracellular matrix proteins discovered in Caenorhabditis elegans, with orthologs in all vertebrate species including human and mouse. Hemicentins share a single, highly conserved amino-terminal von Willebrand A domain, followed by a long （〉40） stretch of immunoglobulin repeats, multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal module. C. elegans has a single hemicentin gene that has pleiotropic functions in transient cell contacts that are required for cell migration and basement membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions and elastic fiber-like structures. Here, we summarize what is known about the function ofhemicentin in C. elegans and discuss implications for hemicentin function in other species.

ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling

The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs within diffe rent domains of the adult neural stem cell niche,the subventricular zone are not well defined.Quiescent NSCs are arranged at the apical ventricular wall,while mitotically activated NSCs are found in the basal,vascular region of the subventricular zone.Here,we found that ADAM 10(a disintegrin and metalloproteinase 10)is essential in NSC association with the ventricular wall,and via this adhesion to the apical domain,ADAM10 regulates the switch from quiescent and undiffe rentiated NSC to an actively prolife rative and differentiating cell state.Processing of JAMC(junctional adhesion molecule C)by ADAM 10 increases Rap1 GAP activity.This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression.Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative prope rties of neural tissue.